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      Ruxolitinib for the treatment of myelofibrosis: its clinical potential

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          Abstract

          Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK) 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF), a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with MF, ruxolitinib recipients exhibited durable reductions in spleen size, reductions in circulating pro-inflammatory cytokines, improvements in physical activity, weight gain, and alleviation of symptoms (including constitutional symptoms) in patients with and without JAK2 mutation. These findings were confirmed by two phase III clinical MF studies, in which a greater proportion of ruxolitinib recipients achieved a spleen volume reduction of ≥35% from baseline at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001) and with best available therapy in the other (31.9% versus 0%; P < 0.0001). Alleviation of MF symptoms and improvements in quality of life were also significantly greater in ruxolitinib recipients. Overall survival of patients treated with ruxolitinib was significantly longer than of those receiving the placebo. Owing to risks of potentially serious adverse effects, eg, myelosuppression, ruxolitinib should be used under close physician supervision. Longer follow-up of the phase III MF studies is needed to reach firm conclusions regarding ruxolitinib’s capacity to modify the natural disease course.

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          Author and article information

          Journal
          Ther Clin Risk Manag
          Ther Clin Risk Manag
          Therapeutics and Clinical Risk Management
          Therapeutics and Clinical Risk Management
          Dove Medical Press
          1176-6336
          1178-203X
          2012
          2012
          01 March 2012
          : 8
          : 95-103
          Affiliations
          [1 ]Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, Zagreb, Croatia
          [2 ]Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
          Author notes
          Correspondence: Srdan Verstovsek, UT MD Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030, USA, Tel +1 713 745 3429, Fax +1 713 794 4297, Email sverstov@ 123456mdanderson.org
          Article
          tcrm-8-095
          10.2147/TCRM.S23277
          3295626
          22399854
          © 2012 Ostojic et al, publisher and licensee Dove Medical Press Ltd.

          This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

          Categories
          Review

          Medicine

          jak2 inhibitor, ruxolitinib, myelofibrosis

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